Many selective agents are known which, when incorporated into biological growth media, allow for the preferential growth (i.e. selection) of particular organisms, especially particular bacteria. It is well-known, for example when performing a bacterial transformation, to incorporate an antibiotic resistance gene on the transforming DNA, and subsequently exposing the mixed population of transformed and untransformed cells to the relevant antibiotic, thereby inhibiting the growth of untransformed cells and selecting for transformed cells.
Equally, it is known to use various dye substances or salts to select for a particular organism (e.g. a pathogen) in a mixed population of bacteria present in a sample obtained from a human or animal subject, as an aid to diagnosis of infectious diseases. However, these selective agents are known to inhibit the growth of healthy cells (Vassiliadis et al, 1974 J. Appl. Bacteriol. 37, 411-418) and to restrict the recovery of injured cells (Kang & Siragusa 1999 Appl. and Env. Microbiol. 65, 5334-5337). This is a severe disadvantage because, in many practical applications, it is desired to recover organisms which are injured or “stressed” (e.g. when attempting to recover pathogens from food samples) due to exposure to sub-optimal conditions (of temperature, pH, or the like).
Allen et al. (1978 Nature 272, 56-58) disclosed that phosphonopeptides possessed antibacterial properties. In particular, the compound L-alanyl-L-1-aminoethylphosphonic acid (called “alaphosphin”) was shown to be a reasonably potent anti-bacterial agent which was believed to cause inhibition of peptidoglycan synthesis. Alaphosphin consists of the L stereoisomer of alanine, coupled to L-1-aminoethylphosphonic acid (AEP), the —COOH group of the alanine and the amino group of AEP condensing to form a peptide bond. These original findings were further developed by Atherton et al. (1979 Antimicrob. Agents and Chemother. 15, 677-683) and by Allen et al. (1979 Antimicrob. Agents and Chemother. 16, 306-313). However, alaphosphin was never widely adopted as an antibiotic, and was not proposed for use as a selective agent. In particular, antibiotics are generally intended to be “broad spectrum”, so as to kill a wide range of bacteria, which renders their use as selective agents in diagnostic microbiology unlikely.